The overall objective of the proposed research is to investigate the nature and structural basis for the basement membrane alterations in the human diabetic eye. By studying the composition and characterizing the components of the basement membrane of retinal vessels and lens capsules from the eyes of normals and diabetics, it is hoped that within this organ compositional and structural differences between the normal and diabetic basement membranes can be uncovered which may explain the pathological consequences of this disease in the eye. Once the composition and components of the basement membranes from normal and diabetic eyes have been characterized, efforts will be made to correlate any observed differences with the severity of the diabetic lesions observed in the tissues and the duration and degree of control of the disease. It is hoped that in this way the relationship between the pathology of the disease in the eye and the chemistry of the basement membrane can be elucidated and some insight obtained as to possible means of minimizing the basement membrane alterations and thus the resulting pathophysiology of the diabetic state. These studies may also help to clarify the relationship between the basement membrane lesions in the diabetic eye and those in the kidney which have morphological and histochemical similarities which may have their basis in the common chemical and immunological properties of the basement membranes in these two organs. The long-term goal of the project is therefore an understanding of the chemical basis of the microangiopathic complications of diabetes using the retinal vasculature as the model system for investigation. We have recently developed methods for the isolation of retinal vessels and the prepartion of pure morphologically intact basement membrane of these vessels from bovine eyes (Meezan et al., 1974 and 1975). In preliminary experiments these methods have been adapted to make possible the preparation of sufficient basement membrane material from one or two human eyes to carry out the analysis and fractionation of basement membrane components on a microscale.